Ligaplants, the next‑generation prosthodontic implants

ligaplants

1. Ligaplants , the Next‑Generation Prosthodontic Implants: A Comprehensive Review Bathla N, Sailo JL, Kapoor N, Nagpal A, Gupta R, Singla A. Ligaplants , the next-generation prosthodontic implants: A comprehensive review. Indian J Dent Sci 2021;13:146-9 Nishu Priya II PGT Journal Club

2. Introduction In today’s era, fixed and removable partial dentures are replaced by implants . Due to lack of periodontal ligament (PDL) inflammation around implant may cause serious bone loss, than does the inflammation around the natural tooth with PDL. This soft, richly vascular, and cellular connective tissue permits forces, elicited during masticatory function, and other contact movements to be distributed to the alveolar process through the alveolar bone proper.

3. DIFFERENCES BETWEEN NATURAL TEETH AND DENTAL IMPLANTS

4. Tissue engineering: foundation of ligaplants Tissue engineering has emerged as a new and ambitious approach that utilizes biodegradable polymers to make scaffolds into the cells to produce tissues in the presence of growth factors. As PDL has been shown to possess immense regeneration capacity, restoring the strength of biomechanical tissue as well as reestablishing the innervations. In this, tissue‑engineered PDL cells are formed on the dental implants thus acting as a natural tooth. This new dimension in the field of implant dentistry is known as ligaplants .

5. Studies have demonstrated that the use of a combination of tissue engineered products with an osteo conductiv e matrix for periodontal regeneration improves the beneficial effect of these materials by accelerating cellular growth and revascularization of the wound site. Regeneration proceeds with a new layer of cementum, attached to original cementum of the tooth root, into which new transverse fibers are integrated. Then, if a new cementum layer were to be laid down on the surface of the engineered-device, this would accommodate the integration of a properly attached PDL with the potential to stimulate the regeneration of adjacent alveolar bone.

6. However, today, tissue engineering has opened a new vista in periodontal regeneration and more so in the treatment of dental implants. From various scaffolds to matrices, all have proved their ability to regenerate the entire periodontium. Lin et al. reported the utilization of autologous rat PDL cells derived from molar tooth root surfaces to regenerate PDL tissues on titanium. They used Matrigel, a three‑dimensional biomatrix scaffold rich in essential extracellular matrix (ECM) components, to facilitate organized rat PDL regeneration at the titanium implant alveolar bone interface.

7. The cultured PDL cells exhibited high proliferation rates, clonogenicity, and formed cementum‑like tissue on the titanium implant surface, and PDL tissue with Sharpey’s fibers inserted perpendicular to the implant.

8. Till now, osseointegrated implants are considered to be the most acceptable implants because of their high long‑term clinical survival rate. These problems could be resolved if implants with PDL could be developed.

9. Procedure of making ligaplants One of the best methods for making Ligaplants is tooth transplantation with double PDL stimulation. The donor tooth is extracted and immediately replanted in its original alveolus, 14 days before transplantation. This trauma triggers a healing process of cell proliferation and differentiation within the PDL. The in vivo cell culture reaches its peak of activity after 14 days. After which the transplantation of the tooth can be carried out, with millions of cells undergoing cell differentiation around the root of the tooth by new Sharpey’s fibers. This model can be used in its biological and clinical aspect, in a similar manner as cell culture around an artificial root, using various tissue‑engineering techniques.

10. Preparation of ligaplants

11. Preparation of temperature‑responsive culture dishes The polystyrene culture dishes are used and N‑isopropylacrylamide monomer in 2‑propanaol solution is spread onto them. Then, the dishes are subjected to electron beam irradiation using an area beam electron processing system. The temperature‑responsive polymer‑grafted (poly- nisopropylacrylamide ) dishes are then rinsed with cold water, and ungrafted monomer is removed and then they are sterilized with ethylene oxide.

12. Interphase of implant and periodontal ligament tissue Tissue-specified uniqueness was acquired after implantation: a new-cementum like layer, typical for regenerated PDL, orientation of cells and fibres across the non-mineralized peri-implant space. Bone formation was induced around ligaplants , suggesting an osteogenic potential of the new PDL.

13. Precautions taken during the preparation of ligaplants The cushion of sufficient thickness favors the formation of PDL and the prolonged cell culturing may cause the occurrence of non‑PDL cell types. To preserve the cell differentiation state and to obtain adequate cell stimulation, the bioreactor should be constructed in such a way that it resembles the PDL situation during the cell growth. The cells are positioned in a narrow space between the ligaplant and surrounding the hollow cylinder. It was thereby expected that the PDL phenotype would be favored implicating a tight attachment of cells to the implant. Hence, during the preparation of the ligaplants , following guidelines need to be followed to obtain the successful ligaplants which brings big improvements to the implant system: Least mechanical movements of the medium flow Space between the implants and culture should be optimal Duration of the surface treatment should also be optimal

14. Studies‑based evidence for ligaplants Many in vitro experiments have demonstrated the formation of cementum‑like tissue with an intervening PDL, when the dental implants were placed in close proximity to the radicular portion of tooth. Gault et al. used ligaplants for tooth replacement. Study - PDL formation was observed and a new layer of tissue resembling repair cementum was formed on the ligaplant surface and the structure of lamina dura resembled that around a natural tooth. Nyman et al . in 1982 suggested that the cells of the PDL possess the ability to reestablish connective tissue attachment Nunez et al. in 2012 further proved the regenerative potential of PDL‑derived cells in a proof of principle study. Takata et al. in an animal study found that, while new connective tissue attachment occurred on bioactive materials such as bioglass and hydroxyapatite, little or no cementum deposition was seen on bioinert materials such as titanium alloy and partially stabilized zirconium. Choi placed implants with the cultured autologous PDL cells and revealed that, after 3 months of healing, a layer of cementum‑like tissue with inserting collagen fibers had been achieved on some implant surfaces. Kano et al. have suggested that implants surrounded by PDL ‑ like tissue could be developed, when immediately after the extraction, tooth‑ shaped hydroxyapatite‑coated titanium implants were placed into the tooth socket where some PDL still remained.

15. Osseo integrated Implants versus Periodontally Integrated Implants ( Ligaplants )

16. Advantages It alleviates problems like gingival recession and bone defects of missing tooth. Mimics natural insertion of natural tooth roots in alveolar process. Ligaplants become firmly integrated without interlocking and without direct bone contact, despite the initial fitting being loose in order to spare PDL cell cushion. Bone formation was induced and movements of ligaplants inside the bone suggests an intact communication between bone and implant surface.

17. Disadvantages The culturing of ligaplants should be done with caution i.e the temperature, the cells that are used for culturing, the duration of the culturing and others. If some difficulty evokes during the culturing, the ligaplants may fail as other nonperiodontal cells may develop. With limited facilities and members to perform this research, the cost of this type of implant is high. The factors affecting the host to accept the implant or the growth of PDL in the socket is unpredictable, which may result in failure of implant.

18. Cementum Formation Around a Titanium Implant: A Case Report Renzo Guarnieri, DDS1/Luciano Giardino, MD, DDS2/Roberto Crespi, DDS3/Roberto Romagnoli, MD, DDS4; (INT J ORAL MAXILLOFAC IMPLANTS 2015;17:729–732

19. Animal studies have shown that a periodontal ligament may be produced around a titanium implant when it is in contact with fractured and retained roots. Formation of cementum and attachment connective tissue around titanium implants confirms that cementum progenitor cells are located in the periodontal ligament, since cementum and periodontal ligament are present at the implant-root interface, whereas the remainder of the implant, which is not in contact with the root, shows osseointegration. The aim was to evaluate histologically the characteristics of the tissue present between a titanium implant and a retained root, which were subsequently extracted as a result of peri-implantitis.

20. Case report The patient was a 40-year-old man who had lost the mandibular right canine because of trauma. After several months, the lost tooth was replaced with an implant positioned in contact with root residue not detected by radiologic examination. One year later, the patient suffered pain and mobility at the implant site. Examination revealed that the implant had degree I mobility with a probing depth of about 8 mm around the entire circumference. Radiologic investigation revealed the presence of a tooth fragment very close to the implant.

21. The sample was sectioned, mounted, and observed under a phase-contrast microscope with the DIC system. Root cementum in the apical zone. Numerous cementocytes are visible (black arrow) adhering to the implant surface (white arrow). There is a clear demarcation line between dentin and neo-cementum apposition on the implant surface . Continuous cementum along the implant surface Enlargement of area shown. Clear demarcation between dentin and layer of neo-cementum

22. Results The periodontal space between the root and the implant was present in the form of a rudimentary space with a continuous layer of cementum strongly adhering to the surface of implant, with no blood vessels or collagen fibers. Cellular cementum and cementocytes

23. Discussion In the clinical case under consideration, a marked presence of root cementum covering the implant surface was seen, but with no connective tissue fibers and no blood vessels in the periodontal space. A previous study has shown that the similar cementum attachment protein (CAP) is capable of recreating putative cementoblastic population on root slices in vitro and therefore might play an important role in cementogenesis during periodontal homeostasis and wound healing.

24. Tissue-engineered ligament: implant constructs for tooth replacement Gault P, Black A, Romette J-L, Fuente F, Schroeder K, Thillou F, Brune T, Berdal A, Wurtz T. Tissue-engineered ligament: implant constructs for tooth replacement. J Clin Periodontol 2010; 37: 750–758

25. Currently, to replace lost teeth without considering the PDL, implants of inert biomaterial are directly inserted into jawbones. In these procedures, local bone defects and generally poor bone quality necessitate bone reconstruction before implantation. A further, commonly observed problem is gingival recession, due to modified tissue architecture, which requires further surgical intervention . An implant system that would include a PDL with tissue-inducing properties might alleviate these problems. I mplants carrying a PDL may be installed in the extraction socket of the missing tooth, thereby facilitating the surgical procedure. Natural implant anchoring might also be compatible with further growth and development of the alveolar bone housing, and it may allow tooth movements during orthodontic therapy.

26. Human clinical investigation Human patients were recruited with the main entry criteria of having one compromised tooth to be replaced, and a radicular area sufficient for PDL cell collection. Research participants were between 35 and 69 years of age, non-smokers, Caucasians, in good general health, and without acute or chronic oral inflammation except in the compromised tooth. Ligaplants were prepared using the protocol without fibronectin coating. After surgery, mechanical probing was performed and radiographs were obtained to study tissue healing. Periodontal pocket depths and ligaplant mobility were recorded by two independent evaluators, following standard periodontal evaluation routines.

27. Results Isolated PDL cells are able to form a new PDL on an apatite surface

28. PDL cells from individual patients were allowed to attach to Ti pins, and implanted into the cell donors.

29. Mechanical resistance around all ligaplants in a millimet er range indicated firm, healthy tissue. In addition, in all cases except one, the probing depth was reduced around the implant, which indicated that the ligaplants had brought about reinforced tissue structure Ligaplant #8 is still in place after 5 years. Bone structure was similar to that around tooth roots; however, trabeculae were rather sparse and thin. A desmodontal gap, corresponding to a PDL space of normal width, was evident around the ligaplant , and the structure of the lamina dura resembled that around a natural tooth Before surgery, root fracture in tooth #34 immediately after ligaplant implantation Partial bone regeneration after 24 weeks After 24 months, note the almost complete replenishment of the major defect Forty-two months; the periodontium has partially restructured

30. Regarding ligaplant #2, radiographs indicated that it moved inside the apparently intact bone. It should be noted that the bone level remained constant, but that the implant moved coronally during the period of observation.

31. Two ligaplants lost anchoring during the first month and were removed, andfive ligaplants had to be removed subsequently at 4, 15, 22, 51, and 52 months. Failures were due to unintended occlusal disturbances and luxation in five cases, and to unknown reasons in two cases.

32. Discussion The ligaplant system mimics the natural insertion of tooth roots in alveolar bone. Tissue-engineered PDL has been obtained starting from a stratified cushion of PDL cells cultivated on HAP-coated Ti pins. Tissue-specific characteristics were acquired after implantation: a new cementum-like layer, typical for regenerated PDL ( Ripamonti 2007), orientation of cells and fibres across the non-mineralized peri-implant space. Currently, evidence concerning the nature of the cementum, PDL, and alveolar bone-like tissue that was formed around ligaplants depends on indirect observations.

33. S upport for cementum resides in the positioning of this tissue along the HAP layer of the ligaplant , its limited thickness, a desmodontal -like space, and the absence of ankylosis. The support for bone induction in the clinical study is based on the radiography results: the appearance of a lamina dura, typical for the alveolar bone around tooth roots, and the trabecular bone around the lamina dura. Ligaplants became firmly integrated without mechanical interlocking and without direct bone contacts, despite the initial fitting being loose in order to spare the PDL cell cushion. Bone formation was induced and movement of ligaplants inside the bone was often observed, suggesting an intact tissue communication between bone and the implant surface.

34. Ethical Applications Ligaplants , a revolutionary new strategy, has been clinically tested in vitro as well as in vivo. Various studies on animals have reported positive results but correlation of results of the in vivo studies are still to be done. As per the strong evidence reported in the literature, this can be the near future of the implant therapy as it can provide the function, form and responses identical to that of the natural teeth.

35. conclusion In conclusion, tissue engineering of the PDL has been achieved as a proof- ofconcept . dentistry has been transformed by the Introduction of periodontal tissue engineering. Based on the modality, ligaplants have been recently introduced to overcome the shortcomings of the conventional implants. Majority of the studies related to the ligaplants , done on the animals has shown successful results but still more achievable and practical way of procuring the periodontal ligament attached implants needs to be introduced. Also more human studies need to be done to evaluate the successful outcome of this strategy. As ligaplants has various advantages in comparison to conventional implants, these can emerge as a new revolutionary addition to the implant dentistry.

36. References Bathla N, Sailo JL, Kapoor N, Nagpal A, Gupta R, Singla A. Ligaplants , the next-generation prosthodontic implants: A comprehensive review. Indian J Dent Sci 2021;13:146-9 Renzo Guarnieri, DDS1/Luciano Giardino, MD, DDS2/Roberto Crespi, DDS3/Roberto Romagnoli, MD, DDS4; (INT J ORAL MAXILLOFAC IMPLANTS 2015;17:729–732 Bathla N, Sailo JL, Kapoor N, Nagpal A, Gupta R, Singla A. Ligaplants , the next-generation prosthodontic implants: A comprehensive review. Indian J Dent Sci 2021;13:146-9 Misch’s contemporary implant dentistry; fourth ed Bioengineered Periodontal Tissue Formed on Titanium Dental Implants; J Dent Res 90(2):251-256, 2011 Saleem M, Kaushik M, Ghai A, Tomar N, Singh S. Ligaplants : A revolutionary concept in implant dentistry. Ann Maxillofac Surg 2020;10:195-7.